In vitro pharmacodynamics of colistin against Acinetobacter baumannii clinical isolates

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Abstract
Colistin is being increasingly used for treatment of infections caused by multidrug-resistant Gram-negative bacteria, including Acinetobacter baumannii. The in vitro pharmacodynamic properties of colistin (sulphate) were investigated by studying the time–kill kinetics and the post-antibiotic effect (PAE) against multidrug-resistant, including colistin heteroresistant, A. baumannii. Time–kill was studied with four multidrug-resistant clinical isolates at concentrations ranging from 0.5 to 64 × MIC. The PAE was examined after 20 min exposure with five clinical isolates, including the four in the time–kill study, plus ATCC 19606. Colistin showed extremely rapid killing in a concentration-dependent manner; but re-growth was observed as early as 3 h and substantial re-growth at 24 h even at concentrations up to 32 × MIC or 64 × MIC for some isolates. Colistin exhibited modest PAE of 1.0, 2.3 and 3.5 h at 16, 32 and 64 × MIC, respectively, against ATCC 19606. Surprisingly, negative PAE (range: –0.8 to –8.15 h) was observed for all of the five clinical isolates. These findings suggest that monotherapy with colistin methanesulphonate, the parenteral form of colistin, and long dosage intervals (e.g. 24 h) may be problematic for treatment of infections caused by colistin heteroresistant A. baumannii.